Growth Hormone Deficiency Research Articles

Development and Validation of a Prediction Model Using Sella Magnetic Resonance Imaging–Based Radiomics and Clinical Parameters for the Diagnosis of Growth Hormone Deficiency and Idiopathic Short Stature: Cross-Sectional, Multicenter Study

Background Growth hormone deficiency (GHD) and idiopathic short stature (ISS) are the major etiologies of short stature in children. For the diagnosis of GHD and ISS, meticulous evaluations are required, including growth hormone provocation tests, which are invasive and burdensome for children. Additionally, sella magnetic resonance imaging (MRI) is necessary for assessing etiologies of GHD, which cannot evaluate hormonal secretion. Recently, radiomics has emerged as a revolutionary technique that uses mathematical algorithms to extract various features for the quantitative analysis of medical images. Objective This study aimed to develop a machine learning–based model using sella MRI–based radiomics and clinical parameters to diagnose GHD and ISS. Methods A total of 293 children with short stature who underwent sella MRI and growth hormone provocation tests were included in the training set, and 47 children who met the same inclusion criteria were enrolled in the test set from different hospitals for this study. A total of 186 radiomic features were extracted from the pituitary glands using a semiautomatic segmentation process for both the T2-weighted and contrast-enhanced T1-weighted image. The clinical parameters included auxological data, insulin-like growth factor-I, and bone age. The extreme gradient boosting algorithm was used to train the prediction models. Internal validation was conducted using 5-fold cross-validation on the training set, and external validation was conducted on the test set. Model performance was assessed by plotting the area under the receiver operating characteristic curve. The mean absolute Shapley values were computed to quantify the impact of each parameter. Results The area under the receiver operating characteristic curves (95% CIs) of the clinical, radiomics, and combined models were 0.684 (0.590-0.778), 0.691 (0.620-0.762), and 0.830 (0.741-0.919), respectively, in the external validation. Among the clinical parameters, the major contributing factors to prediction were BMI SD score (SDS), chronological age–bone age, weight SDS, growth velocity, and insulin-like growth factor-I SDS in the clinical model. In the combined model, radiomic features including maximum probability from a T2-weighted image and run length nonuniformity normalized from a T2-weighted image added incremental value to the prediction (combined model vs clinical model, P=.03; combined model vs radiomics model, P=.02). The code for our model is available in a public repository on GitHub. Conclusions Our model combining both radiomics and clinical parameters can accurately predict GHD from ISS, which was also proven in the external validation. These findings highlight the potential of machine learning–based models using radiomics and clinical parameters for diagnosing GHD and ISS.

Retinal and choroidal microvascular assessment of children receiving recombinant growth hormone therapy

BackgroundThe purpose of this study is to evaluate the retinal and choroidal microvascular state in children with congenital isolated growth hormone deficiency (IGHD) and determine the effect of recombinant human growth hormone treatment on these structures compared with healthy controls.MethodsThe study included children with IGHD under recombinant human GH treatment as group one and another group of healthy controls. Both groups were examined using optical coherence tomography angiography (OCTA). Data concerning superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaris (CC), and retinal thickness were recorded.ResultsThe study included two equal groups of 30 individuals. Both groups had no statistically significant differences in age, gender, weight, or spherical equivalent. However, subjects of group II were taller than those of group I (p = 0.011). OCTA images of the SCP, DCP, and CC vessel density revealed statistically non-significant differences between the two groups.ConclusionChildren receiving recombinant growth hormone therapy showed no changes in the retinal and choroidal microvasculature or macular thickness.Trial registration number1094/03/2024 by Minia University Faculty of Medicine Institutional Review Board. Another registration number is UMIN000055654.

The Pediatric Growth Hormone Deficiency Patient Journey: Identifying Opportunities for Digital Health Interventions.

Pediatric growth hormone deficiency (PGHD) is a chronic condition where the pituitary gland fails to produce sufficient growth hormone, leading to delayed growth and developmental challenges. Patient journey maps can provide insight into pain points and potential opportunities for new or improved interventions to enhance care. However, a patient journey map does not yet exist for PGHD. Secondary data analysis was performed on interviews and focus groups from five cohorts in Sweden, the United Kingdom, Luxembourg, France, and The Netherlands. Participants included 62 patients and caregivers who used a prototype digital health solution, which was used to guide discussions. Grounded theory was used to analyze the data, resulting in a patient journey map comprising six stages: awareness, diagnosis, treatment planning, treatment initiation, treatment maintenance and transition. This provides the first detailed PGHD patient journey map, revealing emotional sensitivities and challenges at each stage, and suggesting areas for targeted interventions to improve adherence and long-term outcomes.

Isolating the direct effects of growth hormone on lifespan and metabolism in mice.

Prior studies have shown that interrupting the growth hormone/insulin-like growth factor-I (GH/IGF-I) signaling axis extends laboratory mouse lifespan, but confounding effects of additional gene or hormone deficiencies that exist in commonly used models of GH/IGF-I interruption obscure the specific effect of GH on longevity. We address this issue by using mice with a specific knockout of the GH gene and show that both males and females on a mixed genetic background display extended lifespans resulting from GH deficiency. Our physiological assessment of these mice revealed that in addition to weighing significantly less and displaying significantly greater body fat (as a percentage of body weight), GH deficient mice display significant impairments in glucose metabolism and preferential fat utilization. These data provide strong evidence that GH deficiency is directly responsible for the altered nutrient utilization and extended lifespan that is commonly observed in mouse models of GH/IGF-I interruption.

Prevalence and determinants of dyslipidemia in 2,338 Dutch childhood cancer survivors: a DCCS-LATER 2 Study.

Childhood cancer survivors (CCS) face an increased risk of early cardiovascular disease. In our nationwide CCS cohort, we assessed the prevalence and determinants of dyslipidemia, a well-established risk factor for accelerated atherosclerosis and cardiovascular disease. Prevalence of dyslipidemia was cross-sectionally assessed in 2,338 adult CCS and compared to adults with no cancer history (Lifelines, n=132,226). Dyslipidemia was defined by multiple classifications as well as lipid abnormalities to investigate the impact on prevalence and determinants. Logistic regression models, adjusted for age, sex, and BMI, were used to assess the cohort effect on presence of dyslipidemia. Determinants of dyslipidemia were identified through multivariable logistic regression. CCS (median age 34.7y, median follow-up 27.1y) had significantly increased odds of dyslipidemia compared to the reference cohort according to all classifications (NCEP-ATP-III, WHO, EGIR, CTCAEv.4.03). In survivors without lipid-lowering agents (n=2,007), lipid abnormalities were present in 20.6% (triglycerides>1.7mmol/L), 30.3% (HDL-c<1.0/1.3mmol/L (male/female)), 29.9% (total cholesterol>5.2mmol/L), 7.3% (LDL-c>4.1mmol/L), and 7.7% (apolipoprotein-B>130mg/dl). Compared to references without lipid-lowering agents (n=126,631), survivors had increased odds of high triglycerides (aOR=1.89, 95%CI=1.68-2.13), low HDL-c (aOR=2.73, 95%CI=2.46-3.03), and high apolipoprotein-B (aOR=1.84, 95%CI=1.53-2.20). Sex, age, BMI, physical activity, abdominal/pelvic, cranial, and total body irradiation, alkylating agents, smoking, growth hormone deficiency, and diabetes mellitus were associated with (≥1 definition of) dyslipidemia in CCS. CCS are at increased risk of dyslipidemia, with various modifiable and non-modifiable determinants identified, underscoring the importance of survivor-specific risk assessment tools to control cardiovascular morbidity and mortality in this high-risk population.

Microglia-derived ADAM9 promote GHRH neurons pyroptosis by Mad2L2-JNK-caspase-1 pathway in subarachnoid hemorrhage

The incidence of growth hormone deficiency (GHD) after subarachnoid hemorrhage (SAH) is significantly higher than that of other neuroendocrine disorders, but the mechanism is still elusive. We used mass spectrometry to identify differentially expressed proteins in cerebrospinal fluid samples from a well-characterized cohort of patients. A total of 683 proteins were identified, including 39 upregulated proteins in the GHD group. ADAM9 was most highly associated with GHD. In vivo, ADAM9 colocalized with M1 microglia markers, GH and cognitive ability of mice decreased significantly, and microglia secreted ADAM9 significantly. ADAM9 regulates pyroptosis of GHRH neurons by the Mad2L2-JNK-caspase-1 pathway. Sorafenib inhibits ADAM9 secretion by microglia and improves GH levels and the cognitive ability of mice. This study found that the crosstalk between GHRH neurons and neuroglial cells in the hypothalamic arcuate nucleus, i.e., microglia, is an essential factor in the formation of GHD in SAH. We propose that neutralization of ADAM9 production by microglia might be a potential therapy for GHD after SAH.Graphical abstract

Growth Hormone Deficiency in Adults

Growth Hormone Deficiency in Adults

Genetic variations, clinical presentation and treatment outcome of isolated growth hormone deficiency type I and II: case series and review of the literature.

To report a case series of four patients with isolated growth hormone deficiency (IGHD) type I from two Chinese pedigrees and to elucidate phenotype-genotype correlation of IGHD type I and II with GH1 gene alterations in the literature. Whole exome sequencing (WES) was performed and a literature review was conducted. Four patients presented with extreme growth retardation (height -4.74 to -6.50 SDS) and undetectable peak growth hormone (GH) during GH stimulating test. WES revealed a novel homozygous nonsense mutation, c.316delC (p.L106Cfs*35), in GH1 gene in the the first pedigree. Deletions of exon 1-5 in GH1 gene were identified in the second pedigree. Ideal catch-up growth after GH treatment was achieved. 94 patients with IGHD type I and 240 patients with IGHD type II were included in literature review. Patients with IGHD type I exhibited younger age (3.2 vs 6.0 years, P < 0.001), more severe growth retardation (median height -6.50 vs -3.84 SDS, P < 0.001), lower peak GH levels (0.05 vs 1.70 ng/ml, P < 0.001) and a higher dosage of GH (0.22 vs 0.17 mg/kg/week, P = 0.012) compared to patients with IGHD type II. Gross deletions constituted 72.3% of IGHD type I cases, while splicing mutations and missense mutations comprised 54.2% and 45.0% of IGHD type II cases. In patients with IGHD type I harboring gross deletion, an early age of diagnosis correlated with both a higher height SDS at diagnosis and a better response after GH treatment. Height SDS after GH treatment in patients with IGHD type II carrying splicing mutations was negatively correlated with age at diagnosis. We identified two GH1 gene mutations, c.316delC (p.L106Cfs*35) and deletions of exon 1-5 in four Chinese patients with IGHD type I. They had a good response to GH treatment and gained satisfactory height improvement. Early diagnosis and initiating treatment may lead to a better prognosis.

Effect of Growth Hormone Treatment on Growth Rates in Patients With Growth Hormone Deficiency, Idiopathic Short Stature, and Small for Gestational Age

Effect of Growth Hormone Treatment on Growth Rates in Patients With Growth Hormone Deficiency, Idiopathic Short Stature, and Small for Gestational Age

The impact of inactivation of the GH/IGF axis during aging on healthspan.

Several mouse lines with congenital growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis disruption have shown improved health and extended lifespan. The current study investigated how inactivating this axis, specifically during aging, impacts the healthspan. We used a tamoxifen-inducible global GH receptor (GHR) knockout mouse model starting at 12 months and followed the mice until 24 months of age (iGHRKO12-24 mice). We found sex- and tissue-specific effects, with some being pro-aging and others anti-aging. Measuring an array of cytokines in serum revealed that inactivation of the GH/IGF-1 axis at 12 months did not affect systemic inflammation during aging. On the other hand, hypothalamic inflammation was significantly reduced in iGHRKO12-24 mice, evidenced by GFAP+ (glial fibrillary acidic protein, a marker of astrocytes) and Iba-1+ (a marker for microglia). Liver RNAseq analysis indicated feminization of the male transcriptome, with significant changes in the expression of monooxygenase, sulfotransferase, and solute-carrier-transporter gene clusters. Finally, we found impaired bone morphology, more pronounced in male iGHRKO12-24 mice and correlated with GH/IGF-1 inactivation onset age. We conclude that inhibiting the GH/IGF-1 axis during aging only partially preserves the beneficial healthspan effects observed with congenital GH deficiency.

The Rising Popularity of Growth Hormone Therapy and Ensuing Orthopedic Complications in the Pediatric Population: A Review.

The utilization of recombinant human growth hormone therapy in pediatric populations, originally approved to treat diseases of growth hormone deficiency, has expanded to encompass a broader range of indications, leading to a threefold increase in its utilization in the last two decades. However, concerns regarding its safety, particularly those that are orthopedic in nature, have grown alongside its increasing popularity. Growth hormone usage has been reported to predispose patients to a multitude of common orthopedic conditions, including carpal tunnel syndrome, Legg-Calve-Perthes disease, little league shoulder, Osgood-Schlatter disease, osteochondritis dissecans, scoliosis, Sever's disease, and slipped femoral capital epiphysis. The pathways by which growth hormone therapy can precipitate orthopedic pathology has been shown to be multifactorial, involving mechanisms such as hormonal changes, growth plate instability, rapid growth, and increased susceptibility to overuse injury. This review examines the orthopedic consequences of growth hormone therapy in pediatric patients by discussing these potential pathophysiologic mechanisms of injury and analyzing subsequent clinical manifestations. By examining processes underlying these complications, we highlight the need for orthopedic surveillance and management in children receiving GHT, particularly those with pre-existing musculoskeletal comorbidities or high levels of physical activity. Our findings underscore the importance of a multidisciplinary approach involving co-management by pediatricians, endocrinologists, and orthopedic surgeons to optimize safety and outcomes for these patients. Directions for future research include correlating pathophysiologic mechanisms to injury patterns, investigating long-term complications in recently approved growth hormone therapy indications, and informing clinical guidelines on the management of orthopedic injuries in this patient population.

The association between metabolite profiles and impaired bone microstructure in adult growth hormone deficient rats

BackgroundAdult growth hormone deficiency (AGHD) is associated with an increased risk of fractures and impaired bone microstructure. Understanding the metabolic changes accompanying bone deterioration in AGHD might provide insights into mechanisms behind molecular changes and develop new biomarkers or nutritional strategies for bone destruction. Our study aimed to investigate the association between altered metabolite patterns and impaired bone microstructure in adult rats with growth hormone deficiency.MethodsThirty seven-week-aged adult Lewis dwarf homozygous (dw/dw) rats (five females and five males), and adult Lewis dwarf heterozygous (dw/ +) rats (five females and five males) rats were compared. Micro-computed tomography (Micro-CT) was used to examine the bone's microstructure. Hematoxylin and eosin (H&E) staining were used to quantify the histological characteristics. Liquid chromatography-mass spectrometry untargeted serum metabolomic analysis was applied in the study. ELISA was used to measure serum bone turnover markers and IGF-1 levels.ResultsAdult dw/dw rats exhibited great reductions in trabecular volume bone density (Tb.vBMD), bone volume/total volume (BV/TV), and cortical thickness (Ct. Th) compared with adult dw/ + rats (all p values < 0.05), indicating significant impairment in bone microstructure. The serum metabolite profiles revealed substantial differences between the dw/dw rats and dw/ + rats. A total of 134 differential metabolites in positive ion mode and 49 differential metabolites in negative mode were identified. Five metabolites, including Lysophosphatidylcholine(LPC) 20:3, LPC22:6, LPC22:4, cortisol and histamine levels were upregulated in dw/dw rats. The steroid hormone biosynthesis and bile secretion pathways were the main perturbed metabolic pathways. There were significant associations between differential metabolites and the impaired bone microstructure parameters, indicating that the selected metabolites might serve as potential biomarkers for deteriorated bone microstructure in AGHD.ConclusionAdult dw/dw rats exhibit impaired bone microstructure and distinct serum metabolic profiles, and the altered metabolites were significantly associated with bone microstructure destruction. This provides a new insight into understanding the mechanism of bone deterioration in AGHD patients from a metabolic perspective.

A clinical review of early assessment for congenital hypothyroidism in newborns

Congenital hypothyroidism is a critical factor associated with stunting, as thyroid hormone deficiencies can impair growth starting in utero. Children with thyroid disorders, including conditions like hypoparathyroidism, often experience growth retardation due to congenital abnormalities and growth hormone deficiencies. For neonates, a lack of thyroid hormones can lead to long-term impacts, such as physical and mental disabilities, neurological disorders, and stunted growth. Early detection of congenital hypothyroidism is, therefore, essential and is typically part of newborn screening aimed at identifying congenital abnormalities. Implementing early screening protocols can diagnose and treat congenital hypothyroidism promptly, mitigating risks such as stunting and enabling better health outcomes for children. This literature review examines methods of early detection for congenital hypothyroidism across various global contexts. Three databases—PubMed, ScienceDirect, and Google Scholar—were searched using a systematic literature review approach, yielding five eligible studies with a combined study population of 920.441 newborns. These studies involved screenings for T4, TSH, 17-OHP, and G-6-PD, identifying hypothyroidism in 2.530 (27%) cases. Screening involved blood samples taken from the umbilical cord or heel within 48 to 72 hours after birth. Understanding early detection procedures for congenital hypothyroidism is essential for nurses, as it enables them to engage in early intervention and provide effective nursing care for affected infants. Early involvement can help prevent the adverse, long-term effects associated with congenital hypothyroidism, improving quality of life and supporting healthy growth trajectories for children at risk. Keywords: Congenital hypothyroidism; literature review; nursing assessment; paediatric nursing; prevention

Somatropin therapy in Italy during 2019-2022: prevalence and incidence rates estimated by data from the national register and regional health sources.

The availability of epidemiological data relating to the therapy with somatropin (recombinant Growth Hormone, rGH) is scarce and mostly limited to specific clinical conditions. In Italy, the National Register of rGH users (Registro nazionale degli assuntori dell'ormone della crescita - Rnaoc) has been established since 2004 as recommended by the Italian medicine agency (Aifa). However, prevalence (P) and incidence (I) estimates in the Italian population are lacking. Data from the Rnaoc and a questionnaire submitted to all the Italian regions have been used to calculate P and I rates of rGH treatment exposure in the Italian paediatric (0-17 years) and adult (≥18 years) population during 2019-2022; P and I rates of growth hormone deficiency (GHD) in paediatric patients have been estimated as well. Results from the two data sources have been compared. In 2019-2022, the estimated P rate in the paediatric population was 13,4/10.000, in adults 0,7/10.000 inhabitants; the I rate was 2,3/10.000 and 0,06/10.000 inhabitants, correspondingly. The estimated P rate of paediatric GHD was 8,9/10.000, the I rate was 1,5/10.000 inhabitants, respectively. Study results showed a better reliability of data collected via questionnaire because more consistent with Italian regional resident populations.

Identification and differentiation of somapacitan, a long-acting growth hormone derivative, and recombinant human growth hormone in equine plasma by LC-HRMS for doping control purpose

Somapacitan, a long-acting growth hormone derivative, and recombinant human growth hormone (rhGH) are protein-based drugs generally used to treat growth disorders and GH deficiency in humans. Due to their potential to enhance the horse performance, the use of these drugs is prohibited at-all-times by the International Federation of Horseracing Authorities for horseracing and the Fédération Equestre Internationale for equestrian sports. In this study, we developed a test method for the identification and differentiation of somapacitan and rhGH in equine plasma by using liquid chromatography high-resolution mass spectrometry (LC–HRMS). The method involved C4 solid-phase extraction after ammonium sulfate precipitation, followed by chloroform/methanol precipitation, trypsin digestion, and analysis by LC-HRMS. The discriminative identification of somapacitan and rhGH was successfully achieved through the detection of their respective unique T10 peptide fragments. Noteworthy, the T10 peptide fragment of somapacitan was detected with its side chain structure remaining intact. The limit of identification (confirmation) (LOI) was determined to be 5 ng/mL for somapacitan and 2 ng/mL for rhGH in equine plasma, while the limit of detection (LOD) was 5 ng/mL for somapacitan and 1 ng/mL for rhGH. Furthermore, using the peptide fragments T1, T8, and T9 (which are shared between somapacitan and rhGH), the presence of somapacitan in equine plasma could be confirmed with higher sensitivity, achieving down to LOIs of 2 ng/mL and LODs of 1 ng/mL. The method was validated with respect to specificity, identification capability, robustness, precision, and reproducibility, paving the way for the analysis of post-administration samples from our already planned administration trials and future potential positive cases.

P41 Decoding short stature in a child with lupus nephritis: an unusual association with de la Chapelle syndrome

Abstract Introduction Recent studies have implicated the dysregulation of epigenetic factors in maintaining favourable lyonization of X-chromosome as a plausible putative mechanism in causing high incidence of systemic lupus erythematosus (SLE) in females. This is reflected by the increased risk of SLE in patients with ‘disorders of sex development’ (DSD) such as Klinefelter’s syndrome (47,XXY). de la Chapelle syndrome (46,XX with SRY gene) is another DSD wherein patients resemble males phenotypically with 2 X-chromosomes in their karyotype. Herein, we report the diagnostic and therapeutic challenges in a case of juvenile-onset SLE with refractory lupus nephritis and concomitant association of de la Chapelle syndrome. Case description A 13-year-old boy presented with history of chronic febrile inflammatory polyarthritis involving small and large joints for 6-months. On examination, he had short stature, and swelling, tenderness and restriction of movement of the proximal and distal interphalangeal joints, wrist and shoulder joints of both sides. Investigations revealed elevated erythrocyte sedimentation rate with normal C-reactive protein. Routine urine microscopy examination was suggestive of proteinuria. Further immunological investigations revealed hypocomplementemia, positive anti-nuclear antibody (4+, homogeneous pattern) and elevated titres of anti-double stranded DNA. He was also noted to have positive direct coomb’s test and antiphospholipid antibodies. His renal biopsy was suggestive of lupus nephritis (Class II). Based on the above constellation of clinical and laboratory parameters, a diagnosis of SLE with lupus nephritis (Class II) and musculoskeletal involvement was proffered. He was started on oral prednisolone (2 mg/kg/day followed by taper), hydroxychloroquine (5 mg/kg/day) and sun protective measures. However, persistence of proteinuria after 3-months necessitated addition of mycophenolate mofetil (1200 mg/m2/day) following which his SLE-disease activity went into remission. Notwithstanding the control of SLE-disease activity, there was no improvement in his height after 1-year of follow-up. A pediatric endocrinology consultation for short stature revealed features of idiopathic growth hormone (GH) deficiency and primary hypogonadism. Chromosomal analysis was suggestive of 46,XX karyotype, and fluorescence in situ hybridisation revealed ‘XX’ pattern with SRY gene located on one of the X chromosomes. He was commenced on recombinant GH therapy for 18-months following which his height improved. At 2-years of follow-up, he developed worsening proteinuria. A repeat renal biopsy was suggestive of class-IV lupus nephritis. However, he responded poorly to 6-doses of monthly intravenous cyclophosphamide (500 mg/m2/dose). Considering refractory lupus nephritis, he was commenced on rituximab [(375 mg/m2/dose) at 0 and 2-weeks] following which his proteinuria became passive. He remains well on follow-up. Discussion SLE in DSD has been more frequently described in the context of Klinefelter’s syndrome (47, XXY), implicating the X chromosome as a putative mechanism in its pathogenesis. However, the clinical profile and outcome of SLE in patients with de la Chapelle syndrome has not been explored extensively. de la Chapelle syndrome (46, XX with SRY gene), first described in 1964, is a rare DSD with a reported prevalence of 1/20000 to 1/25000 newborn males. The clinical phenotype includes decreased body height, gynecomastia, maldescended testis and other features of hypogonadism including infertility. Chagnon et al reported the first patient of SLE in de la Chapelle syndrome. Authors described a 19-year-old man who presented with features of SLE since early childhood. His disease was complicated by severe rash, mucositis, arthritis, focal proliferative glomerulonephritis, transaminitis and refractory thrombotic thrombocytopenic purpura, and osteoporosis (including growth failure). In addition, he also had primary hypogonadism with normal GH. Dillon et al also reported another 46, XX male with presence of SRY gene. However, the clinical details including treatment were not elucidated in this paper. Both these patients were phenotypically male due to the presence of SRY gene, similar to the index patient. Our patient’s difficult clinical course with arthritis, growth failure and refractory lupus nephritis, and primary hypogonadism was similar to the patient reported by Chagnon et al. The treatment protocol of SLE in DSD is not well-established. Chagnon et al reported using corticosteroids, hydroxychloroquine, methotrexate, intravenous pulse cyclophosphamide, azathioprine, and plasmapheresis. The index patient was treated similarly; however, due to refractory lupus nephritis, he was also given rituximab. To the best of our knowledge, this is the first report of successful use of anti-CD20 therapy in SLE with DSD such as de la Chapelle syndrome. Key learning points • This case highlights the challenges in diagnosis and management of patients with DSD including de la Chapelle syndrome. The main learning point from this case was that short stature in juvenile-onset SLE in a boy with features of primary hypogonadism warrants further evaluation. As reported in previous literature, this subset of patients may not respond adequately to conventional first-line therapy. The need for escalation of therapy or primary therapy with rituximab in such patients needs further exploration. Another point of concern is using cyclophosphamide, a known drug to have adverse effect on testes, in these patients since it may further compromise testicular function.

High-coverage targeted lipidomics revealed novel profile of serum lipid dysregulation in adult growth hormone deficiency.

Patients with adult growth hormone deficiency (AGHD) are at increased risk of metabolic syndrome. Despite extensive research efforts in recent decades, the lipid metabolism pattern of AGHD has yet to be thoroughly characterized. In this study, we used lipidomics analysis of fasting serum samples from 30 AGHD patients due to intracranial germ cell tumors (iGCTs) and 30 age-, gender-, and body mass index (BMI)-matched healthy controls to investigate the serum lipidomic pattern of AGHD patients due to iGCTs. We meticulously quantified 534 serum lipids from 29 classes using high-coverage targeted lipidomics technology in conjunction with a robust bioinformatics pipeline. Our results revealed an AGHD-specific dynamic change in serum lipidomic profile, manifested by higher overall levels of many lipid subclasses, including triacylglycerols (TAGs), diacylglycerols (DAGs), phosphatidylglycerols, phosphatidylethanolamines (PE), phosphatidylcholines (PC), phosphatidylinositols, ceramides, and bis(monoacylglycerol)phosphates than in healthy controls, and a distinct lowering level in alkyl PE (PE-O) and alkyl PC (PC-O). AGHD individuals with non-alcoholic fatty liver disease showed specific changes in higher TAG and DAG subclass levels. Alterations in lipid profiles may contribute to metabolic dysregulation in AGHD patients. TAGs, PCs, and PE-fatty acids positively correlated with BMI, fasting insulin, insulin resistance index, and adverse lipid parameters. In contrast, ether-linked PE-O, PC-O, and LysoPE-O showed a negative correlation. This study has significantly expanded the current understanding of lipid dysregulation in AGHD patients due to iGCT. These findings can potentially guide future research and the development of monitoring and intervention strategies.

The effect of 30 min of supine rest on plasma renin concentrations in paediatric patients.

The aim of this study is to interpret plasma renin concentrations (PRCs) correctly in a clinical setting, it is essential to understand to what extent physical activity influences the concentration. Reference values for different postural positions exist for adults, but data for children are sparse. In this study, the effect of 30 min of rest on plasma renin concentrations in paediatric patients was examined. In total, 41 paediatric patients, undergoing either arginine or clonidine provocation tests for growth hormone deficiency, were included. For each stimulation test, two blood samples were drawn. One at time 0 min and one after 30 min of rest. In total, renin concentrations were determined in 86 serum samples. Renin concentrations decreased from 0 to 30 min with a median value of -20.5% (inter-quartile range: -33.0% to -12.8%). This decrease was not dependent on sex, age, medication or comorbidity, and the variance of renin did not differ between 0 and 30 min. Renin concentrations in children differ according to postural position, which is comparable to adults. Thus, the clinical interpretation of renin results needs to consider the preanalytical conditions applied in the local reference population.

Comparison of the effectiveness of prepubertal growth hormone treatment on height and predicted adult height in children with short stature born small for gestational age vs. with a growth hormone deficiency.

We compared the effects of growth hormone (GH) treatment on height and predicted adult height in children with short stature born small for gestational age (SGA-SS) vs. with a growth hormone deficiency (GHD). This retrospective study analyzed the background and clinical characteristics of children who presented to Tanaka Growth Clinic for short stature and were diagnosed with either SGA-SS or GHD and underwent treatment with GH. We compared differences in height, height velocity, GHdose increases, insulin-like growth factor-1 levels, and bone-age/chronological-age ratio between the two groups. Out of these children, 33 SGA-SS and 54 GHD children started GH treatment before the age of 8 years, witha mean dose of 0.25 mg/kg/week and 0.20 mg/kg/week, respectively. At treatment initiation, the age and height standard deviation scores (SDS) of the SGA-SS group were significantly lower than those of the GHD group. The height velocity was significantly greater in the SGA-SS group for 3 years owing to higher GH doses and younger age. No notable differences in puberty onset height or predicted adult height were observed between the two groups for boys or girls. The increase in height SDS from the start of GH treatment until the onset of puberty was substantially greater in the SGA-SS group than in the GHD group for both sexes. Adult height of patients with SGA-SS is expected to resemble that of patients with GHD but may notreach the-1.0 SD achieved with GH treatment of those patients in Western countries.

Comparison of growth hormone stimulation tests in prepubertal children with short stature according to response to growth hormone replacement.

Growth hormone (GH) stimulation tests are essential tools for diagnosing GH deficiency (GHD). We aimed to compare L-dopa, insulin, and arginine-induced stimulation tests based on response to GH replacement. We retrospectively collected data from a review of patients who underwent the GH stimulation test. A total of 138 patients diagnosed with idiopathic short stature were categorized into group I. The remaining 135 patients, who were diagnosed with GHD and treated for 1 year, were classified into 2 subgroups: group IIa, consisting of patients with an increase of at least 0.5 in height standard deviation score (SDS), and group IIb, patients with an increase of less than 0.5 in height SDS. At the initial visit, group IIa exhibited significantly lower insulin-like growth factor binding protein-3 (IGF-BP3) and higher body mass index (BMI) SDS compared to the other groups. Following 1 year of treatment, group IIb showed significantly lower height SDS, height SDS gain, growth velocity, predicted adult height SDS, weight SDS, and a higher insulin-like growth factor-1 SDS than group IIa. Bone age and IGF-BP3 were inversely associated, and BMI SDS and IGF-BP3 were positively associated with height SDS gain in GHD patients. The specificity and accuracy rates were 50.3% and 70.3% for the L-dopa-induced stimulation test, 72.3% and 86.6% for the insulin tolerance test (ITT), and 64.7% and 87.2% for the arginine-induced stimulation test (ArST). The ArST demonstrated lower specificity compared to the ITT. However, patients undergoing ArST experienced fewer side effects, suggesting that a careful selection of stimulation tests is crucial in diagnosing GHD.